Background: Transcriptional factors (TFs) are responsible for orchestrating gene transcription during cancer progression. However, their roles in gastric cancer (GC) remain unclear.Methods: We analyzed the differential expressions of TFs and, using GC cells and tissues, investigated plexin C1 (PLXNC1) RNA levels, as well as PLXNC1's clinical relevance and functional mechanisms. The molecular function of PLXNC1 was evaluated in vitro and in vivo. Kaplan-Meier curves and the log-rank test were used to analyze overall survival (OS) and disease-free survival (DFS).Results: PLXNC1 was frequently up-regulated in GC and associated with poor prognosis. The expression level of PLXNC1 could serve as an independent biomarker to predict a patient's overall survival. Notably, knockdown of PLXNC1 significantly abolished GC cell proliferation, and migration, and overexpression of PLXNC1 accelerated carcinogenesis in GC. The gene set enrichment analysis (GSEA) indicated that high-expression of PLXNC1 was positively correlated with the activation of epithelial-mesenchymal transition (EMT), TNF-α, and IL-6/STAT3 signaling pathways. PLXNC1 promoted proliferation and migration of GC cells through transcriptional activation of the interleukin 6 signal transducer (IL6ST), which could rescue the malignant behavior of PLXNC1-deficient GC cells. Conclusions:Our study demonstrated that the PLXNC1 plays an oncogenic role in GC patients. The PLXNC1-IL6ST axis represents a novel potential therapeutic target for GC.
Transcription factors represent the crucial role of controlling gene transcription in cancer development and progression. However, their functions in gastric cancer have not been thoroughly characterized. For this study, we comprehensively evaluated the correlation between infiltration patterns of tumor microenvironment (TME) cells and TFs expression in the cohort of stomach adenocarcinoma (STAD) from TCGA database. We integrally explored differential expression panel and prognostic value of candidate TFs in TCGA‐STAD cohort. Notably, we found a key transcription factor named HEYL, which its expression level was correlated with stromal component transformation of TME. HEYL was regularly high expressed in gastric cancer and correlated with patients’ poor prognosis. Knockdown of HEYL prominently abrogated the tendency of cell proliferation, migration, and progression in gastric cancer. Consistently, overexpression of HEYL strikingly accelerated the gastric carcinoma development through activating oncogenic signaling pathways and transcriptional activation of cadherin 11 (CDH11). Our findings not only identified the close relationship between TFs and TME phenotype, but also emphasized the crucial importance of TFs, especially HEYL, which could be identified as a candidate biomarker to evaluate prognostic risk and therapeutic effect in gastric cancer.
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